pediatric anemias · pediatric anemias gábor kovács md, phd semmelweis university 2nd dep. of...

PEDIATRIC ANEMIAS

Gábor Kovács MD, PhD

Semmelweis University

2nd Dep. of Pediatrics

Diagnosis of anemia

Age Hemoglobin (g/l)

6 mo - 2 years < 100

< 110

6 - 14 years < 120

Adult women < 120

Adult man < 130

2 - 5 years

CLASSIFICATION OF ANEMIAS

MICROCYTAER

HYPOCHROM

NORMOCYTAER

NORMOCHROM

MACROCYTAER

(MCV<75 fl

MCH<27 pg)

(MCV 75-90 fl

MCH>26 pg)

(MCV>90 fl)

Iron deficiency hemolysis megaloblastosis

(B12-, folic acid def.)

Thalassemia secunder anemia alcohol, liver disease

Chronic. Illnes Blood loss MDS, aplastic anemia

Plumb intox. Bone marrow insuff. CDA

sideroblastyc (B6) Renal failure gravidity, myxoedema

Reticulocyte

Increased: hemolytic anemias, blood loss,

regeneration

Decreased: bone marrow diseases,

erythropoietine deficiency, other

deficiencies (iron, Vitamin B12, folic acid)

„Normal”: ineffective erythropoesis

(thalassemia, MDS, CDA, myelofibrosis),

chr. inflammation, malignancy

RDW

Red cell distribution width (SD)

Normal: 10-14 %

increased: iron deficiency, cong. membrane

disorders, burn, thrc. aggregation-s./DIC

Microcytaer anemias

Iron Protoporphyrine

iron deficiency anemia

chr. infection sideroblastic

malignancy anemia

thalassemia

Hem + globin

Hemoglobin

DD of hypochrom (mikrocytaer)

anemias

iron def. inf, tumor thalassemia siderobl.

MCV

MCH

MCHC

all

decreased

slightly

decreased

all

decreased

decreased

(MCV might

be increased)

SeFe decreased decreased norm. increased

TVK increased decreased norm. norm.

ferritin decreased norm. or

increased

norm. increased

iron reserve decreased norm. or

increased

norm. norm. or

increased

Hb electro-

phoresis

norm. norm. pathol. norm.

Thalassemia

Thalassemia

Iron deficiency anemia

Hypochrom anemia

(iron deficiency)

Daily iron requirement

4 mo - 1 year 1.0 mg

2 - 10 years 0.5-1.0 mg

Puberty 2.0 mg

Adult man 1.1 mg

Adult women 2.4 mg

Pregnant women -6 mg

Stages of iron deficiency

Iron depot

Transport

iron

Hb-iron

Normal iron homeostasis:

Malt train med II/3

Stages of iron deficiency

Prelatent iron deficiency:

Iron stores

are empty

Decreased serum ferritine; decreased

transferrine saturation; increased IBC;

hemoglobin normal

Iron depotTransport iron

Hb-iron

Malt train med II/5

Stages of iron deficiency

Latent iron deficiency:

Transport

iron

decreased

Decreased serum ferritine; decreased transferrine

saturation; decreased serum iron, increased IBC;

increased erythrocyte protoporphyrine, hemoglobin

normal

Iron depotTransport iron

Hb-iron

Malt train med II/6

Stages of iron deficiency

Iron deficiency anemia:

Iron depotTransport iron

Hb-iron

Microcytaer, hypochrom anemia

Malt train med II/7

Decreased serum ferritine; decreased transferrine

saturation; decreased serum iron, increased IBC;

increased erythrocyte protoporphyrine, decreased

hemoglobin and MCH

Iron deficiency

Hb low

MCV<75 fl

MCH<27 pg

RDW>14 %

Anisocytosis

Thr>400

No infections

+ anamnesis

PS: in Down-s: MCV and MCH higher

Iron def.

Significance of iron

Important for the synthese of

hemoglobin and myoglobin.

Basic for the oxydative phosphorilation

(energy supply).

Important for the normal mental

functions and for the immune system.

The dopaminerg system

normal: Iron def.:

D-2 rec. sensitivity

dopamine effect

opiate effect

Learning

capacity

dopamine

opiate effect

Learning

capacity

Malt train med II/46

Iron and the immune system

Iron def.

Lymphocyte proliferation

Interleukin-2

Immune response

Malt train med II/54

Causes of iron deficiency 1.

Decreased iron intake:

Nutritional intake insufficient: not

enough iron in the meal, breast-feeding

after 6 months.

Decreased absorption: gastrointestinal

diseases, malabsorption

Causes of iron deficiency 2.

Increased iron need:

Chronic blood loss: ulcus, varix, GI

malignancy, colitis, diverticulosis,

menstruation, parasitosis, hematuria.

Increased need: prematurity, growth,

gravidity, breast feeding.

Acute bleedings: Hemorrhagic

diathesis, coagulation disorders.

Incidence of iron deficiency - USA

•Infants: 14 %

•3-5 y: 4 %

•Adolescents (girls): 9-11 %

•Women, 20-49 y: 9 %

AAP guideline 2010

Preterm infants

1 mo-12 mo: 2 mg/kg Fe/day

(drug or Fe-rich formula)

Pediatrics: 2010, 126: 1040-1051

AAP guideline 2010

Brest-feeding infants

>4 mo: 1 mg/kg/day extra Iron

Until, half of the daily food is Fe-rich-

food or Fe-rich-formula

AAP guideline 2010

Formula-feed infants

Need: 10-11 mg/day iron

In formula Iron m in. 10-12 mg/l

Until, half of the daily food is Fe-rich-

food.

NO cow milk until 1 year!!

AAP guideline 2010

1-3 years

Daily need: 7-8 mg

Iron-rich food!

Screening at 1 year: ferritin, CRP, Hb

Later screening: for risk groups (14 %)

Risk groups

•Preterm infants, SGA newborns

•Only breast feeding after 4 mo (!)

•Cow milk <1 y

•Low iron intake

•Growth retardation

•Nutritional and absorption

problems

•Girls at puberty, heavy menses

bleedings

AAP guideline 2011 for adolescents

12-15 y: 9 % iron deficiency, 2 % anemia

26-29 y: 11 % iron deficiency, 3 % anemia

Boys< 1 % (more iron needed at puberty)

Risk group: strong menses bleeding, chr.

illness, malabsoprtion, obesity, sportsmen,

veggie diet (veganism)

AAP guideline 2011 for adolescents

Daily need: 9-13 y: 9 mg, 14-18 y: girls 15

mg, boys 11 mg

Gravid adolescents: 27 mg

For girls: yearly blood picture vérkép

(ferritin, CRP, Hb)! (in boys only 1x)

If Hb< 110 g/l, treatment!!: 3-6 mg/kg

per os iron

Treatment of iron deficiency

Malt train med II/40

Treatment of iron deficiency 1.

Disadvantage: gastrointestinal

intolerance (nausea, vomitus, diarrhoea,

obstipation)

Uncontrolled absorption.

Benefit: cheap, good absorption,

quick effect.

Iron-salts (sulfate)

Receptor-mediated, controlled absorption.

Advantage:

Few side effects.

Decreased risk for free radicals.

But slower and lower effect!

Iron-carbohydrate-complex

Treatment of iron deficiency 2.

Iv: 1-2 mg/kg/d for 5 days

Dose: 5-6 mg/kg/d orally

Timing: orally for 4-6 months (!)

Treatment of iron deficiency 3.

Normocytaer anemias

Classification of anemias 2.

B. Hemolysis

1. Intracorpuscular or intrinsic

membrane-defects (spherocytosis, elliptocytosis,

stomatocytosis PNH)

hemoglobinopathy (sickle cell anemia, thalassemia)

enzyme-defekts (pentóz-monofoszfát ciklus

zavarai, glutation szint. zavarai)

Classification of anemias 3.

B. Hemolysis

2. Extracorpuscular or extrinsic

immunmechanisms:

natural isoagglutinins (transzfusion rection)

aquired antibodies (autoimmun hemol. anemias)

drugs

infection diseases (mononucleosis, mycoplasma)

autoimmune or malignant diseases

Clinical signs of hemolysis

Pallor, collapse

Icterus

Splenomegaly

Cholelithiasis

Others: ulcus cruris, aplastic crisis, cyanosis, cardiopulmonal dysfunktion, colica, waist pain, fever, adenopathy,

Emergency!!!

Laboratory signs of hemolysis

serum indirect bilirubin increased

urinary urobilinogene increased

hemoglobinuria

serum haptoglobine decreased

reticulocytosis (10-20%)

elevated serum LDH

fragmented RBC-s

erythroid hyperplasia in the bone marrow

Spherocytosis

Elliptocytosis

Stomatocytosis

Sickle cell disease

Cold agglutination

RBC fragmentation (DIC)

Treatment of hemolytic anemias

Spherocytosis – ery transfusions, splenectomy

Immune hemolysis – IVIG (warm AIHA),

steroid, rituximab (cold AIHA)

Sickle cell – fluid, analgetic

Thalassemia: transfusion, chelate, BMT

DIC – fresh frozen plasma (+treatment of the

etiology)

Drug-induced hemolysis

Immune complex binding

quinine, phenacetin

Drug-adsorption

penicillin, cefalosporins

Non-specific adsorption

Membrane disturbances, decreased ery

lifespan

Auto-antibodies (Coombs positive)

alfa-metildopa, pentostatin, fludarabin,

tacrolimus, alfa-interferon

Other secunder hemolytickus állapotok

INFECTIONS

malária, clostridium, viruses

CHEMICAL, PHYSICAL FACTORS

drugs, chemicals, heavy metals (lead, cupper,

iron), burn

SECUNDER

liver-, kidney diseases

SUMMARY

All non-mikrocyter anemia should

be treated in hematological centers!

All microcyter anemia, not-

responding for a 2-4 weeks of iron

therapy, should be admitted to the

center!

Macrocytaer anemias

Macrocytosis

Bone marrow insufficiency

Hypoplastic anemia: only anemia

(decreased erythropoesis)

Aplastic anemia: pancytopenia (decreased

erythro-, myelo, thrombopoesis)

Cong. aplastic anemias

Fanconi anemia

Dyskeratosis congenita

Shwachmann-Diamond s.

Constitucional aplastic anemia

Fanconi anemia

DNS repair defect

(AR, chr. 9 and 20)

Multiple anomalies:

growth stunting,

ment. ret, bone,

kidney, heart, gonad,

skin pigmentation

Dyskeratosis congenita

X-rec. inheritance

In 90% aplastic anemia

Nail dystrophy, mucosal leukoplakia,

hyperpigmentation etc.

Mental retardation

Frequent carcinom

Dyskeratosis congenita

Shwachman-Diamond sy.

AR inheritance

Neutropenia

In 25% aplastic anemia

Metaphyseale chondrodysplasia

Exocrine pancreas insufficiency

Hypoplastic anemias

Cong. red cell aplasia (Diamond-

Blackfan anemia)

Transient eryhtroblastopenia

Parvovirus-induced eryhtroblastopenia

Pure red cell aplasia

Diamond-Blackfan anemia

AD, AR inheritance

Anemia in the 1st year of life

Cong. malformations in 25 %

Normochrom, macrocyter anemia, low

reticulocyte, HbF and EPO increased

In the BM: E:M=1:50

Treatment of congenital anemias

glucocorticoid

ATG

Bone marrow transplantation